雷帕霉素对大鼠神经病理性疼痛及脊髓背角神经元凋亡的影响

被引：6

作者：

冯涛

陈功

丁洁

黄凤贞

机构：

[1] 深圳市宝安区中心医院麻醉科

来源：

山西医科大学学报 | 2017年 / 48卷 / 12期

关键词：

雷帕霉素; 神经病理性疼痛; 自噬; 细胞凋亡;

D O I：

10.13753/j.issn.1007-6611.2017.12.008

中图分类号：

R965 [实验药理学];

学科分类号：

100602 ; 100706 ;

摘要：

目的研究鞘内注射雷帕霉素对大鼠神经病理性疼痛及脊髓背角神经元凋亡的影响。方法雄性SD大鼠30只随机分为假手术组(sham组)、脊神经结扎组(SNL组)和雷帕霉素组(Rap组),每组10只。各组大鼠L4-5鞘内置管后,SNL组和Rap组大鼠结扎左侧腰5脊神经建立神经病理性疼痛模型,sham组大鼠则仅分离暴露左侧腰5神经。Rap组大鼠于术后30 min鞘内注射雷帕霉素0.1μg/10μl,sham组和SNL组则给予注射等容溶剂(5%DMSO)。每日1次,连续7 d。各组大鼠测量术后1,3,5,7 d机械痛阈(paw withdrawal threshold,PWT)和热痛阈(paw withdrawal latency,PWL)。术后第7天处死大鼠并立即取左侧L5节段脊髓背角,电镜下观察神经元自噬体(n=3);Western blot法检测自噬相关蛋白LC3、神经元特异性蛋白Neu N以及凋亡相关蛋白a-caspase3表达(n=7)。结果与sham组比较,SNL组大鼠PWT和PWL在术后第1天和第3天开始分别明显降低,且持续到术后第7天(P<0.05),术后第7天PWT、PWL分别为(12.5±1.0)g和(7.8±0.4)s,较sham组分别降低67%和44%(P<0.05);而脊髓背角LC3Ⅱ和a-caspase3表达分别增高96%和359%(P<0.05),Neu N表达降低21%(P<0.05);与SNL组比较,Rap组大鼠各相应时间点PWT和PWL明显增高(P<0.05),术后第7天PWT、PWL分别为(24.9±1.6)g和(11.8±0.8)s,较SNL组分别增加99%和51%(P<0.05);而脊髓背角LC3Ⅱ和Neu N表达增高44%和19%(P<0.05),a-caspase3表达降低27%(P<0.05)。电镜下Rap组脊髓背角神经元自噬体较SNL组可见较多自噬体。结论雷帕霉素能减轻神经病理性疼痛,其机制可能与雷帕霉素增加脊髓背角神经元自噬,减少神经元凋亡有关。

引用

页码：1236 / 1240

页数：5

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